The objective of this project is to gain insight into the mechanisms underlying the changes in expression of the beta-adrenergic receptors induced by agonists, antagonists, and antidepressant drugs. In the investigation of carbamazepine-induced changes in beta-adrenergic receptor mRNA levels in rat C6 glioma cells, we have focused on the effects of carbamazepine on the homeostasis of calcium and cAMP. cAMP regulates the transport of cholesterol to the mitochondria in the process of neurosteroid biosynthesis. Intracellular free calcium regulates the metabolic function of mitochondria. Mitochondrial benzodiazepine receptor ligands stimulate mitochondrial replication. Carbamazepine and other mitochondrial benzodiazepine ligands induce increases in cAMP and beta-adrenergic receptor mRNA levels. Elevated cytoplasmic calcium inhibits cAMP production. We are pursuing the possibility that carbamazepine can modulate calcium influx in C6 glioma cells from voltage-gated calcium channels through a G-protein coupled mechanism.